4.
Forkhead box M1 (FOXM1) <ul><li>A transcription factor </li></ul><ul><li>Involved in cell proliferation and apoptosis </li></ul><ul><li>Affects the development and function of many organs </li></ul><ul><li>A key cell cycle regulator of both the transition from G 1 to S phase and the progression to mitosis </li></ul>

13.
Matrix metalloproteinase(MMP) <ul><li>Endopeptidases </li></ul><ul><li>Capable of degrading all kinds of extracellular matrix proteins </li></ul>wikipedia.org The main substrates of the gelatinases are type IV collagen and gelatin It has reported that MMP-9 expression is elevated in the liver of FoxM1B trangenic mice

14.
Previous research <ul><li>Alterations in FoxM1 signaling are associated with tumorigenesis </li></ul><ul><li>Overexpression of FOXM1 has been found in a variety of aggressive human carcinomas including pancreatic cancer </li></ul><ul><li>FoxM1 signaling is known to control cell migration and invasion, which are important processes involved in tumor development and metastasis </li></ul><ul><li>The precise role and the molecular mechanism of action of FoxM1 in PC remain unclear </li></ul>

15.
The aim in this article Whether FoxM1 could be an effective therapeutic target for PC ?

16.
Methods and Results <ul><li>To test the consequences of down-regulation and up-regulation of FoxM1 in PC, using: </li></ul><ul><li>siRNA </li></ul><ul><li>cDNA </li></ul>

34.
To examine whether the down-regulation of FoxM1 could lead to a decrease in MMP-2 and MMP-9 activity in PC cells Fig.5 ELISA

35.
<ul><li>Down-regulation of FoxM1 decreased MMP-2 and MMP-9 gene transcription and their activities </li></ul><ul><li>Overexpression of FoxM1 by cDNA transfection led to an increase in MMP-2 and MMP-9 expression and activity (data not shown) </li></ul>

36.
To investigate whether FoxM1 siRNA has any effect on reducing the level of uPAR (urokinase-type plasminogen activator receptor), which are able to regulate the MMP-9 activity in PC Fig.5 FoxM1 siRNA reduced uPAR gene transcription and translation

37.
To test the effects of FoxM1 down-regulation on PC cell migration and invasion, using BD BioCoat Tumor Invasion Assay System www.bdbiosciences.com

45.
Conclusion The down-regulation of FoxM1 could potentially be an effective therapeutic approach for the inactivation MMP-2, MMP-9, and VEGF, which is likely to result in the inhibition of cell growth, migration, invasion, angiogenesis, and metastasis of PC.

46.
Discussion <ul><li>FoxM1 gene is up-regulated in PC due to transcriptional regulation by the Sonic Hedgehog ( 音猬因子 ) pathway </li></ul><ul><li>Sonic hedgehog homolog (SHH) is one of three proteins in the mammalian hedgehog ( 刺猬因子 ) family </li></ul><ul><li>It plays a key role in regulating vertebrate organogenesis </li></ul><ul><li>SHH remains important in the adult. It controls cell division of adult stem cells </li></ul><ul><li>SHH is involved in vascularization of certain embryonic tissues as well as in inducing angiogenesis in an adult mammalian system </li></ul>www.bdbiosciences.com